Bis-(carboxydiphenylamine)-sulfides and sulfones



Patented Nov. 28, 1950 BIS (CARBOXYDIPHENYLA-MINE) SULFIDES ANDSULFONES Alan August Goldberg, Somerset, and Harold Silas Turner, Manchester, England, assignors -to Ward, Blen'kinsop & Company Limited, London, England, a British company No Drawing. Application October 24, 1947, Se-

rial No. 782,013. In Great Britain August 23, 1946 3 Claims. (Cl. 260397.6) l 2 This invention relates to bis-(diphenylamine The products obtained in accordance with the 2-carboxy1ic acid) derivatives having the general formula terest. The new sulphone has valuable antibac- I terial properties of the kind encountered with NH@XA T -NH I p.p-diaminodiphenyl sulphone but it is more soluble and of lower toxicity. The products have H GOOH been found to possess high antitubercle activity. in which X is a sulphide or a sulphone group, t The following examples illustrate the manner sulphur atom of X being dire tl linked to a in which the invention may be carried into effect: clear carbon atom of each of the phenyl residues II and III. More particularly, the invention relates to the new 4:4-bis-(2"-carboxyp-henylamino) diphenyl sulphide and sulphone and to the production thereof.

According to the present invention, there are provided products of pharmacological value having the aforesaid general formula.

Example 1 41 gms. of 4:4-diaminodiphenylsulphone, 26 gms. of o-chlorobenzoic acid, 29 gms. of potassium carbonate and a trace of copper powder are heated under reflux in 200 cos. of amyl alcohol in an oil bath for 3 hours. The reaction mixture is cooled and the amyl alcohol removed by distilla- According to the present invention, a process tion in steam. The res dual aqueous solution is for the production of a compound having the filtered with charcoal, acidified, and the precipiabove general formula comprises reacting the tate redissolved in 2.5 litres of water by addition corresponding p-p-diaminodiphenyl sulphide or of the minimal necessary amount of sodium hysulphone with an ortho-halogenobenzoic acid. droxide solution. This solut on is boiled with The reaction is preferably carried out in a suitcharcoal, filtered and the acid precipitated by adable solvent in the presence of an acid acceptor dition of dilute hydrochloric acid to the boiling and a catalyst. Preferred acid acceptors are the solution. The reprecipitation process is repeated alkali metal carbonates such as potassium carand the green powder thus obta ned extracted bonate in excess over that required for salt forwith 60 cos. of boiling alcohol, the extract filtered mation and a preferred catalyst is copper powder. with charcoal and finally evaporated to small vol- Other sources of copper such as copper salts may ume; on cooling 4:4-bis-(2"-carboxyphenylamalso be used. A suitable solvent is one which 0118- 30 ino) diphenylsulphone separates in fawn prisms solves or partially dissolves one or both of the rem.pt. 258-260 C.

t glcctglhctssand pre-erred solvents are butyl or amyl Exampzle 2 In carrying out the process of the invention a 103 31115. of D pp y p 156 convenient procedure is to heat the reactants, the 30 sins. of O-ChIOIObeIIZOiO acid, 152 0f P catalyst, the acid acceptor and the solvent tosium carbonate and a trace of copp powder are gether, to remove the solvent by suitable means heated with 1 litre of amyl alcohol in an atmossuch as by addition of water and distillation in phere of nitrogen at atmospheric pressure in an steam and to acidify the resulting aqueous soluoil bath at 140 C. for 2 hours. The a y alcohol tion of the formed dialkali metal salt of the prod- 49 is removed by distillation in steam, the residual not with mineral acid in order to precipitate the aqueous solution diluted to 6 litres, boiled with required product. It is advantageous to stir the charcoal, filtered, ac dified at the boiling point reaction mixture and to operate at the boiling and the green precipitate collected. This is then pomt of thesolvent employed in order to obtain redissolved in 5 litres of water containing 70 gms. efiicient mixing. In certains cases, for example, of potassium carbonate, the solution filtered with when one reactant is a sulphide, it is desirable charcoal and reprecipitated as before. The dried to carry out the reaction in the presence of an light green solid (151 g.) is boiled with alcohol, inert atmosphere, such as an atmosphere of nifiltered to remove insoluble blue impurity theretrogen in order to avoid oxidation by atmospheric from and the filtrate refluxed with charcoal and y enfiltered. The solvent is distilled off until its volinvention are of considerable pharmaceutical inume is reduced to about 2.5 litres: on cooling, 4 :4'-bis- (2' -carboxyphenylamino) diphenylsulphide separates as a yellow crystalline powder m.pt. 256-258 C. (decomp.) (found: M.230.5. C26H2004N2S requires M228) We claim:

1. As a new product a bis-(diphenylamine 2- carboxylic acid) derivative having the general formula ing of sulphide and sulphone groups, the sulphur 1 atom of X being directly linked to a nuclear carbon atom of each of the phenyl residues II and HI 2 4:4'-bis- (2' '-carboxypheny1amino) diphenylsulphone.

4 3. 4:4 -bis- 2' -carboxyphenylamino) diphenylsulphide.

ALAN AUGUST GOLDBERG. HAROLD SILAS TURNER.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,003,842 Spiegler June 4, 1935 2,151,543 Zerweck et a1 Mar. 21, 1936 OTHER REFERENCES Chemical Abstracts, vol. 26 (1932), page 2184 (Abstract of Sergeev, J. Gen. Chem, U. S. S. R.. vol. 1 (1931), pp. 279-288. 

1. AS A NEW PRODUCT A BIS-(DIPHENYLAMINE 2CARBOXYLIC ACID) DERIVATIVE HAVING THE GENERAL FORMULA 